Administration of Sulfatide to Ameliorate Type I Diabetes in Non-Obese Diabetic Mice

To explore whether or not inhibition of protein kinase C βII (PKC βII) stimulates angiogenesis as well as prevents excessive NETosis in diabetics thus accelerating wound healing. Streptozotocin (STZ, 60 mg/kg/day for 5 days, i.p.) was injected to induce type I diabetes in male ICR mice. Mice were treated with ruboxistaurin (30 mg/kg/day, orally) for 14 consecutive days. Wound closure was evaluated by wound area and number of CD31-stained capillaries. Peripheral blood flow cytometry was done to evaluate number of circulating endothelial progenitor cells (EPCs). NETosis assay and wound tissue immunofluorescence imaging were done to evaluate the percentage of neutrophils undergoing NETosis. Furthermore, the expression of PKC βII, protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and histone citrullation (H3Cit) were determined in the wound by Western blot analysis. Ruboxistaurin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in ruboxistaurin-treated diabetic mice. Moreover, ruboxistaurin treatment significantly decreases the percentages of H3Cit+ cells in both peripheral blood and wound areas. This prevented excess activated neutrophils forming an extracellular trap (NETs) formation. The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment. The expressions of PKC βII and H3Cit+, on the other hand, decreased with ruboxistaurin treatment. The results of the present study suggest that ruboxistaurin by inhibiting PKC βII activation, reverses EPCs dysfunction as well as prevents exaggerated NETs formation in a diabetic mouse model; thereby accelerating the wound healing process.

Download Full-text

Prevention of type I diabetes in nonobese diabetic mice by virus infection

Science ◽

10.1126/science.3277269 ◽

1988 ◽

Vol 239 (4839) ◽

pp. 500-502 ◽

Cited By ~ 105

Author(s):

M. Oldstone

Keyword(s):

Virus Infection ◽

Type I Diabetes ◽

Type I ◽

Diabetic Mice ◽

Nonobese Diabetic ◽

Nonobese Diabetic Mice

Download Full-text

Contribution of Trem2 Signaling to the Development of Painful Diabetic Neuropathy by Mediating Microglial Polarization in Mice

10.21203/rs.3.rs-671471/v1 ◽

2021 ◽

Author(s):

Xin Chen ◽

Yue Le ◽

Wan-you He ◽

Jian He ◽

Yun-hua Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Neuropathy ◽

Mechanical Allodynia ◽

Type I Diabetes ◽

Intraperitoneal Administration ◽

Thermal Hyperalgesia ◽

Lumbar Spinal Cord ◽

Type I ◽

Painful Diabetic Neuropathy ◽

Diabetic Mice

Abstract Background Painful diabetic neuropathy (PDN) is a common and intractable complication of diabetes mellitus, with little effective treatment. PDN has been associated with spinal neuroinflammation characterized by microglial activation. Recently, the triggering receptor expressed on myeloid cells 2 (TREM2), specifically localized on microglia, has been identified as a vital factor in modulating neuroinflammation and microglial phenotypes in neural diseases. Therefore, we hypothesized that spinal TREM2 might contribute to PDN and neuroinflammation by regulating microglial activity and phenotypes. Methods Type I diabetes mellitus was elicited by a single intraperitoneal administration of streptozotocin (STZ) in mice. The pain behaviors were reflected by paw mechanical withdrawal thresholds (PMWT) and thermal withdrawal latency (PTWL). Results We demonstrated that up-regulation of microglial TREM2 and amplification of both microglial M1 and M2 response was along with the presence of diabetes-related mechanical allodynia and thermal hypersensitivity. Moreover, we found that overexpression of TREM2 in microglia aggravated the symptom of PDN, amplified microglia M1 response, and suppressed microglia M2 polarization in the lumbar spinal cord of diabetic mice. However, inhibition of TREM2 with anti-TREM2 neutralizing antibodies attenuated mechanical allodynia and thermal hyperalgesia in diabetic mice. Besides, we identified Galectin-3 (GLT-3) as the potential ligand of the TREM2 receptor in facilitating the progression of PDN. Conclusions TREM2 could be a critical microglial membrane molecule that modulates microglial phenotypes pain hypersensitivity in PDN. GLT-3 might act as a specific ligand to trigger TREM2 signaling in PDN or other neuropathic pain.

Download Full-text

In vivo antidiabetic activity of aqueous and ethyl acetate leaf extract of Senna singuena (Delile) in alloxan induced diabetic mice

The Journal of Phytopharmacology ◽

10.31254/phyto.2017.6204 ◽

2017 ◽

Vol 6 (2) ◽

pp. 84-92

Author(s):

Njogu M. Stephen ◽

◽

Arika M. Wycliffe ◽

Machocho K. Alex ◽

Ngeranwa J.N. Joseph ◽

...

Keyword(s):

Ethyl Acetate ◽

Plant Extract ◽

Leaf Extract ◽

Type I Diabetes ◽

Intraperitoneal Administration ◽

Scientific Data ◽

Hypoglycemic Activity ◽

Antidiabetic Activity ◽

Type I ◽

Diabetic Mice

The folkloric claims that Senna singuena confers antidiabetic effect to prescribed patients has received long term clinical application accompanied by limited scientific data in support of such claims. This study aimed at bioscreening for hypoglycemic activity of the aqueous and organic fractions of S. singuena in alloxan induced diabetic mice. Type I diabetes mellitus was induced in mice by intraperitoneal administration of alloxan monohydrate followed by graded doses of the aqueous and ethyl acetate leaf extract administered to the experimentally diabetic mice following an overnight fast. The composition of the various phytochemicals of the plant extract was quantitatively assessed using standard procedures. Oral and intraperitoneal administration of the aqueous and ethyl acetate leaf extract caused a significant reduction in plasma glucose level in a dose independent manner in both fractions. The hypoglycemic activity could be attributed to phytoconstituents found in the plant extract. The generated data supports the folkloric claims associating S. singuena with hypoglycemic effects. However, there is need for further studies on this plant to investigate the mechanism of its activity and determine its safety profiles in order to explore possibilities of developing a new antidiabetic drug.

Download Full-text

Regulation of Renal Laminin in Mice with Type II Diabetes

Journal of the American Society of Nephrology ◽

10.1681/asn.v1091931 ◽

1999 ◽

Vol 10 (9) ◽

pp. 1931-1939 ◽

Cited By ~ 1

Author(s):

TAE-SUN HA ◽

JEFFREY L. BARNES ◽

JENNIFER L. STEWART ◽

CHEOL W. KO ◽

JEFFREY H. MINER ◽

...

Keyword(s):

Type Ii Diabetes ◽

Type I Diabetes ◽

Diabetic Mouse ◽

Basement Membranes ◽

Northern Analysis ◽

Type I ◽

Type Ii ◽

Diabetic Mice ◽

Remodeling Of Extracellular Matrix

Abstract. This study examines the regulation of renal laminin in thedb/dbmouse, a model of type II diabetes characterized by extensive remodeling of extracellular matrix. Immunohistochemistry demonstrated an increase in the contents of laminin chains including β1 chain in the mesangium and tubular basement membranes at 1,2,3, and 4 mo of diabetes. Immunofluorescence with an antibody against the recently discovered laminin α5 chain showed that in the normal mouse, the protein had a restricted distribution to the glomerular and tubular basement membranes with scant expression in the mesangium of older mice. In the diabetic mouse, the laminin α5 chain content of the glomerular and tubular basement membranes was increased, with marked expression in the mesangium. Northern analysis revealed a significantdecreasein the renal cortical contents of α5, β1, and γ1 chain mRNA in the diabetic mice compared to control, at each of the time points.In situhybridization showed decreased abundance of α5 transcripts in the glomeruli of diabetic mice compared to nondiabetic controls. Analysis of mRNA changes by Northern andin situhybridization studies demonstrated that the reduction in laminin transcripts involved both glomerular and tubular elements. These observations demonstrate that laminin accumulation in thedb/dbmice with type II diabetes is due to nontranscriptional mechanisms. Because previous investigations in rodents with type I diabetes have shown that the increase in renal laminin content was associated with a corresponding increment in laminin chain transcript levels, it appears that the mechanisms underlying augmentation in renal matrix laminin content may be distinct in the two types of diabetes.

Download Full-text

Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.714440 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jane E. Sinclair ◽

Conor J. Bloxham ◽

Han Chiu ◽

Keng Yih Chew ◽

Jake Russell ◽

...

Keyword(s):

Diabetes Mellitus ◽

Virus Infection ◽

Type I Diabetes ◽

Cardiovascular Complications ◽

Left Ventricular ◽

Cardiac Complications ◽

Type I ◽

Diabetic Mice ◽

Infected Control ◽

Creatine Kinase Mb

People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected control mice, infected diabetic mice had increased serum cardiac troponin I and creatine-kinase MB, left ventricular structural changes and right ventricular functional alterations, providing the first experimental evidence of type I diabetes increasing risks of influenza-induced cardiovascular complications.

Download Full-text

Tauroursodeoxycholic Acid Protects Retinal and Visual Function in a Mouse Model of Type 1 Diabetes

Pharmaceutics ◽

10.3390/pharmaceutics13081154 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1154

Author(s):

Jieming Fu ◽

Moe H. Aung ◽

Megan C. Prunty ◽

Adam M. Hanif ◽

Lauren M. Hutson ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Mouse Model ◽

Visual Function ◽

Type I Diabetes ◽

Retinal Function ◽

Type I ◽

Diabetic Mice ◽

Optomotor Response ◽

Preclinical Research ◽

Tauroursodeoxycholic Acid

Purpose: Previous studies demonstrated that systemic treatment with tauroursodeoxycholic acid (TUDCA) is protective in in vivo mouse models of retinal degeneration and in culture models of hyperglycemia. This study tested the hypothesis that TUDCA will preserve visual and retinal function in a mouse model of early diabetic retinopathy (DR). Methods: Adult C57BL/6J mice were treated with streptozotocin (STZ) and made diabetic at 8–10 weeks of age. Control and diabetic mice were treated with vehicle or TUDCA starting 1 or 3 weeks after induction of diabetes, and were assessed bimonthly for visual function via an optomotor response and monthly for retinal function via scotopic electroretinograms. Results: Diabetic mice showed significantly reduced spatial frequency and contrast sensitivity thresholds compared to control mice, while diabetic mice treated early with TUDCA showed preservation at all timepoints. A-wave, b-wave, and oscillatory potential 2 (OP2) amplitudes decreased in diabetic mice. Diabetic mice also exhibited delays in a-wave and OP2-implicit times. Early TUDCA treatment ameliorated a-wave, b-wave, and OP2 deficits. Late TUDCA treatment showed reduced preservation effects compared to early treatment. Conclusions: Early TUDCA treatment preserved visual function in an STZ-mouse model of Type I diabetes. These data add to a growing body of preclinical research that may support testing whether TUDCA may be an effective early clinical intervention against declining visual function caused by diabetic retinopathy.

Download Full-text